Patients with myasthenia gravis have autoantibodies against acetylcholine receptor which cause defective neuromuscular transmission as well as anti-myofibrillar antibodies, some binding to myosin, which are related to the presence of thymoma. The initiation of the autoimmune state is unknown. The myasthenic thymus is not only histologically abnormal, containing exessive numbers of B-cells in germinal centers but also contains myoid cells which may auto-sensitize in myasthenics. Using of cytochemical and immunocytochemical techniques will allow us to compare the relative density of myoid cells in myasthenic thymus as compared to normal young thymus of rodents to assess the presence of recptor and myofibrillar antigens on these cells and to evaluate humoral and cell-mediated immunity to these in myasthenics. We will also evaluate the mechanisms by which D-Penicillamine initiates a reversible autoimmune condition almost identical to myasthenia gravis. D-Penicillamine treated acetylcholine receptor shows altered ligand binding related to a conformational change but we must establish the relationship of this to development of new antigenic determinants either haptenic or producing a helper effect.